Levine discusses the important role of precisely regulating gene expression
during animal development. The Drosophila embryo provides a model system
because during early embryogenesis a syncytium with about 6000 synchronously
dividing nuclei is formed before membranes are laid down to separate the nuclei
and areas of regulated gene expression are created. These regions of specific gene
expression ultimately determine the body plan of the organism.
In Part 1 of his lecture, Levine emphasizes the importance of enhancers
in regulating localized gene expression. Enhancers are elements located up or
downstream from the transcription start site of a gene and they bind activators
and repressors of gene expression. By integrating the effect of activators and
repressors, enhancers produce sharp on/off boundaries of gene expression.
In Parts 2 and 3, Levine describes mechanisms used in the embryos to
maintain the precision and robustness of gene expression. One mechanism
is “shadow enhancers”. These are secondary enhancers found at a significant
distance from the transcription start site that act in conjunction with primary
enhancers to ensure the sharp patterns and reproducibility of gene expression. A
second mechanism of ensuring precise activation of gene expression is “Paused
Polymerase”. Active RNA polymerase II binds to the transcription start site, makes
a very short nascent transcript and then pauses. When activators bind to the
promoter, pol II is ready to go and is rapidly activated across many nuclei. When
used together, shadow enhancers and paused pol II provide rapid, uniform, robust
and reproducible gene activation.
In the fourth part of his talk, Levine focuses on the role of repressors in
regulating gene expression. He shows data from his lab that explain the mechanism
of action of the Snail and Polycomb repressors.
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